This study investigates the potential of natural curcuminoids, including pure curcumin, demethoxycurcumin, and bisdemethoxycurcumin, to modulate the human *MDR-1* gene expression in multidrug-resistant human cervical carcinoma cell line, KB-VI. The researchers used Western blot analysis and RT-PCR to assess the effects of these curcuminoids on MDR-1 gene expression. The results showed that all three curcuminoids inhibited MDR-1 gene expression, with bisdemethoxycurcumin exhibiting the most significant effect. Commercial-grade curcuminoid mixtures (77% curcumin, 17% demethoxycurcumin, and 3% bisdemethoxycurcumin) also decreased MDR-1 gene expression in a dose-dependent manner, showing similar inhibitory effects to the natural mixtures. Treatment of drug-resistant KB-VI cells with curcumin increased their sensitivity to vinblastine, which was consistent with a decrease in MDR-1 gene product, a P-glycoprotein. The study suggests that bisdemethoxycurcumin is the most active curcuminoid for modulating MDR-1 gene expression and that curcuminoids could be promising lead compounds for designing more effective MDR modulators.This study investigates the potential of natural curcuminoids, including pure curcumin, demethoxycurcumin, and bisdemethoxycurcumin, to modulate the human *MDR-1* gene expression in multidrug-resistant human cervical carcinoma cell line, KB-VI. The researchers used Western blot analysis and RT-PCR to assess the effects of these curcuminoids on MDR-1 gene expression. The results showed that all three curcuminoids inhibited MDR-1 gene expression, with bisdemethoxycurcumin exhibiting the most significant effect. Commercial-grade curcuminoid mixtures (77% curcumin, 17% demethoxycurcumin, and 3% bisdemethoxycurcumin) also decreased MDR-1 gene expression in a dose-dependent manner, showing similar inhibitory effects to the natural mixtures. Treatment of drug-resistant KB-VI cells with curcumin increased their sensitivity to vinblastine, which was consistent with a decrease in MDR-1 gene product, a P-glycoprotein. The study suggests that bisdemethoxycurcumin is the most active curcuminoid for modulating MDR-1 gene expression and that curcuminoids could be promising lead compounds for designing more effective MDR modulators.